title: Induction of glandular stomach cancers in Helicobacter pylori-infected Mongolian gerbils by 1-nitrosoindole-3-acetonitrile.
abstract: Helicobacter pylori (H. pylori) infection and high intake of various traditional salt-preserved foods are regarded as risk factors for human gastric cancer. We previously reported that Chinese cabbage contains indole compounds, such as indole-3-acetonitrile, a mutagen precursor. 1-Nitrosoindole-3-acetonitrile (NIAN), formed by the treatment of indole-3-acetonitrile with nitrite under acidic conditions, shows direct-acting mutagenicity. In the present study, NIAN administration by gavage to Mongolian gerbils (MGs) at the dose of 100 mg/kg two times a week resulted in three adduct spots (1.6 adducts/10(8)  nucleotides in total), detected in DNA samples from the glandular stomach by (32) P-postlabeling methods. Treatment with six consecutive doses of 100 mg/kg of NIAN, two times a week for 3 weeks, induced well-and moderately-differentiated glandular stomach adenocarcinomas in the MGs at the incidence of 31% under H. pylori infection at 54-104 weeks. Such lesions were not induced in MGs given broth alone, broth + NIAN or infection with H. pylori alone. Thus, endogenous carcinogens formed from nitrosation of indole compounds could be critical risk factors for human gastric cancer development under the influence of H. pylori infection.
authors.affiliation: Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsubara
authors.forename: Shinji
authors.initials: S
authors.lastname: Takasu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
authors.forename: Shuichi
authors.initials: S
authors.lastname: Masuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
mesh_terms: D000097:Acetonitriles / Q000008:administration & dosage*; D000230:Adenocarcinoma / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000821:virology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D003043:Cocarcinogenesis; D018736:DNA Adducts / Q000378:metabolism; D004334:Drug Administration Schedule; D005756:Gastritis / Q000382:microbiology / Q000473:pathology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000473:pathology; D016480:Helicobacter pylori; D008297:Male; D013047:Specific Pathogen-Free Organisms; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000821:virology*
chemical_list: D000097:Acetonitriles; D018736:DNA Adducts; C053072:1-nitrosoindole-3-acetonitrile